Influence of thermal drive on central sleep apnea in the preterm neonate.

BACKGROUND: The incidence of apnea in neonates depends on a number of factors, including sleep state and thermoregulation. OBJECTIVE: To assess the role of thermal drive (body heat loss [BHL]) in the mechanisms underlying short episodes of central apnea during active and quiet sleep in neonates. MATERIAL AND METHOD: Twenty-two neonates (postconceptional age: 36.3 +/- 0.9 weeks) were exposed at thermoneutral (incubator temperature: 32.5 degrees C), warm (34.2 degrees C), and cool (30.4 degrees C) conditions during 3 consecutive morning naps. Oxygen consumption (VO2), skin and rectal temperatures, and central apnea were scored during active sleep and quiet sleep. The thermal drive was expressed as BHL calculated using indirect partitional calorimetry. RESULTS: As expected, apnea occurred more frequently in active sleep than in quiet sleep (P < 0.001). The frequency of apnea in active sleep was higher in the warm condition (P < 0.05). In contrast, apnea episodes were less frequent (P < 0.05) and shorter (P < 0.05) for cool exposure, during which VO2 and rectal temperature increased. The frequency (P < 0.001, r2 = 0.31), mean (P < 0.05, r2 = 0.06), and maximum (P < 0.001, r2 = 0.19) durations of apnea were correlated with the BHL: the greater the BHL (body cooling), the less frequent and the shorter the apnea episodes. In contrast, no relationship between apnea and mean skin or rectal temperature was observed. CONCLUSION: Apneic events were more closely related to BHL than to body temperatures. In cool exposure, the decreases in the duration and frequency of apneic episodes suggest that these events depend on the metabolic drive (which is proportional to energy expenditure).

A reproducible means of assessing the metabolic heat status of preterm neonates.

The aim of the present study was to validate the measurement of metabolic heat production using partitional calorimetry (PC) in preterm neonates exposed to a near-thermoneutral environment in an incubator. In order to reduce experimental uncertainty (due to the different variables involved in the calculation of body heat exchanges between the infant and the environment), the mean radiant temperature and the heat transfer coefficients for convection, radiation and evaporation were measured using a multisegment, anthropometric thermal mannequin which represents a small-for-gestational-age neonate (body surface area: 0.150 m2; simulated birth weight: 1500 g). The metabolic heat production calculated by PC was compared with the results of indirect respiratory calorimetry, which is rarely done in clinical setting since this method interferes with the neonate's environment and requires a high degree of technical preparedness. The oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in 20 preterm neonates exposed to thermoneutral (32.3 degrees C) and to slightly cool environments (30.2 degrees C). The mean skin temperature was measured by infrared thermography. The measurements were made during well-established periods of active and quiet sleep. Metabolic heat production was assessed by weighting each value of VO2 and VCO2 by the duration of the sleep stages. Our results showed that there was no significant difference between the two methods in terms of their estimation of metabolic activity at thermoneutrality (mean overall difference: 0.34 kJ h(-1) kg(-1)) and in the cool environment (0.26 kJ h(-1) kg(-1)). We observed significant interneonate variability. Partitional calorimetry enabled the prediction of body growth with a daily error of less than 5.3 g (2.38 kJ h(-1) kg(-1)) for all the neonates at thermoneutrality and for 85% of the subjects (3.03 kJ h(-1) kg(-1)) in the cool environment. Despite this limitation, we demonstrate here that PC provides reliable information for calculating the energy expenditure of individual preterm neonates on the basis of standard environmental input variables. We suggest that the technique can be advantageously used to assess the energy expenditure and normal growth of these infants.

Effect of caffeine on peripheral chemoreceptor activity in premature neonates: interaction with sleep stages.

Caffeine is widely used for the treatment of apnea in premature neonates. However, the localization of caffeine's target site (central nervous system and/or peripheral chemoreceptors) is not well defined, especially for sleeping neonates whose sleep stages interact with respiratory control. The aim of this study was to assess the activity of the peripheral chemoreceptors in relation to sleep stages in premature neonates treated (or not) with caffeine for idiopathic apnea. Peripheral chemoreceptor activity was assessed in 22 neonates (postconceptional age of 36 +/- 1 wk with birth weights ranging from 790 to 1,910 g) by performing a 30-s hyperoxic test during active and quiet sleep. Eleven neonates received caffeine treatment (4.0 +/- 0.5 mg.kg(-1).day(-1)) and 11 served as controls. For all neonates, the decrease in minute ventilation observed during hyperoxia was greater during active than during quiet sleep. Neonates receiving caffeine showed a significantly greater decrease in ventilation during hyperoxia in both sleep stages, compared with controls (caffeine; -29.7 +/- 12.8% vs. control; -22.0 +/- 7.4%; F(1,15) = 4.6, P = 0.04). We conclude that caffeine administration increases the effectiveness of chemoreceptor activity. Because sleep stage durations were not affected by the treatment, it is likely that the decrease in apneic episodes typically observed with caffeine therapy is only related to respiratory processes and is independent of the sleep stage organization.

Relationship between functional residual capacity and oxygen desaturation during short central apneic events during sleep in "late preterm" infants.

Apneic episodes are frequent in the preterm neonate and particularly in active sleep (AS), when functional residual capacity (FRC) can be decreased. Furthermore, FRC may be inversely correlated with the speed of blood-O(2)-desaturation. We evaluated the potential involvement of FRC in the mechanisms responsible for blood-O(2)-desaturation during short central apneic events (>3 s) in "late-preterm" infants and analyzed the specific influence of sleep state. Apneic events were scored in 29 neonates (postmenstrual age: 36.1 +/- 1.2 wk) during AS and quiet sleep (QS). FRC was measured during well-established periods of regular breathing. Apneas with blood-O(2)-desaturation (drop in SpO(2) >5% from the baseline, lowest SpO(2) during apnea: 91.4 +/- 1.8%) were more frequent in AS than in QS, whereas no difference was seen for apneas without desaturation. The magnitude of the FRC did not depend on the sleep state. In AS only, there was a negative relationship between FRC and the proportion of apneas with desaturation. Even in late preterm infants who do not experience long-lasting apnea, blood-O(2)-desaturation during short apneic events is related (in AS but not QS) to a low baseline FRC. Sleep stage differences argue for a major role of AS-related mechanisms in the occurrence of these apneas.

Ventilatory response to a hyperoxic test is related to the frequency of short apneic episodes in late preterm neonates.

Chemoreception is frequently involved in the processes underlying apnea in premature infants. Apnea could result from a decrease in carotid body effectiveness. However, increased carotid body activity could also initiate apnea through hypocapnia following hyperventilation when the receptors are stimulated. The aim of this study was to analyze the relationship between carotid body effectiveness and short apneic episodes in older preterm neonates. Carotid body effectiveness was assessed at thermoneutrality in 36 premature neonates (2.07 +/- 0.26 kg) by performing a 30-s hyperoxic test during sleep, the oxygen inhalation involving a ventilation decrease. Blood O(2) saturation (Sp(o2)) and ventilatory parameters were monitored before and during the hyperoxic test. Short episodes of apnea (frequency and mean duration) were recorded during the morning's 3-h interfeeding interval. Pretest Sp(o2) was not related to any of the measured respiratory parameters. A higher frequency of short apneic episodes was linked to a greater ventilation decrease in response to the hyperoxic test (rho = -0.32; p = 0.01). Increased carotid body response is correlated with greater apneic episodes frequency, even in the absence of concomitant oxygen desaturation. Fetal or early postnatal hypoxemia could have increased peripheral chemoreceptor activity, which could initiate a "overshoot/undershoot" situation, which in turn could induce a critical P(o2)/P(co2) combination and apnea.

Thermoregulatory control of feeding and sleep in premature infants.

OBJECTIVE: The aim of the present study was to test the thermoregulatory feeding control hypothesis in sleeping, premature infants. RESEARCH METHODS AND PROCEDURES: In premature infants, the energy supply from food intake is crucial for (in order of importance): organ operation, body homeothermia, and optimal growth. The Himms-Hagen model of thermoregulatory feeding control involving activation of heat production by brown adipose tissue (BAT) was formulated on the basis of work in (awake) rats. This hypothesis has also been put forward for the human neonate, which can also use BAT to produce metabolic heat. According to the model, feeding episodes occur during a transient increase in body temperature. Feeding is initiated by a dip in blood glucose concentration after sugar uptake by activated BAT. RESULTS: In 14 neonates (bottle-fed on demand), food intake always took place during an increase in skin temperature (+0.19 +/- 0.21 degrees C). Awakening occurred 18 +/- 17 minutes after the minimum skin temperature level had been reached. When feeding time was imposed, feeding was not necessarily situated during an increase in skin temperature, and the sleep duration after food intake increased significantly (+43%). This could be considered as an adaptive response to the short-term sleep deprivation and/or stress elicited by an imposed feeding rhythm. DISCUSSION: The validity of the model supports the use of on-demand feeding in neonatal care units, in accordance with the infant's physiological body temperature oscillations.

Use of the oculocardiac reflex to assess vagal reactivity during quiet sleep in neonates.

Arousal from sleep can be a protective response to life-threatening stimuli. Hence, faults within state-switching processes may lead to fatal events. To investigate the role of the nervous system during cardiac failure triggered by phasic, vagally mediated stimulation, we analysed autonomic and behavioural reactions in 50 premature neonates during quiet sleep (QS) -- a sleep state characterized by a preponderance of tonic, parasympathetic activity. Bradycardia was induced with a standardized ocular compression test. Neither awakening nor behavioural escape reactions were observed during or after an episode of bradycardia. Eighty-six per cent of the provoked bradycardic episodes induced central apnoea. During QS, the neonates' respiratory response and arousability were found to be time-dependent: when the test was performed early in the QS episode, apnoea was more frequent (94%), and no sleep state change occurred. When ocular compression was performed in the later part of the QS episode, a transition towards active sleep was observed, together with significantly fewer episodes of apnoea (64%). These results indicate that a progressive decrease in the respiratory system's responsiveness to phasic, parasympathetic stimulation occurs during QS, whereas arousability increases. Our study suggests that newborns could be more vulnerable to potentially fatal events during the initial portion of a QS episode.

Thermal acclimation of neonates to prolonged cool exposure as regards sleep stages.

The thermal responses of neonates during a cool acclimation period were studied with regard to sleep stages. Sleep stages, body temperatures and metabolic rate (VO2) were studied for seven neonates nursed in incubators and exposed to a cool temperature (thermoneutrality minus 2 degrees C) for 75 h. Each recording session lasted 3 h in the morning: firstly under thermoneutral baseline conditions, then during the first and last 3-h periods of the cool acclimation and finally during the last 3 h of a 24-h recovery period. Sleep structure was modified during the initial hours of cool exposure: the percentage of active sleep increased (AS: +13%, P = 0.028) at the expense of quiet sleep (QS: -11%, P = 0.043). This alteration in sleep structure persisted at the end of the acclimation period. Metabolic heat production only increased in the later period of cool acclimation. Throughout the cool exposure, VO2 increased more (P = 0.040) in QS (+33%) than in AS (+20%) so that by the end of the cool period, VO2 levels were similar in both sleep stages. During cool acclimation, the maintenance of homeothermy is related not only to a change in sleep organization but also to modifications in the thermoregulatory processes in both sleep stages. Considering the importance of AS/QS patterns in the neurobehavioral development of neonates, the present results could have clinical implications for the thermal management of neonates.